Current Research and Activities Dr. Don Kyle, Adjunct Professor of - - PowerPoint PPT Presentation

• Dr. Don Kyle, Adjunct Professor of Pharmacology

and Physiology, OSU Center for Health Sciences

Current Research and Activities

National Center for Wellness & Recovery

“To inspire hope and to develop innovative, science-driven treatment interventions to improve the lives of those afflicted by pain and substance use disorders”

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MISSION

Ending Addiction and Managing Pain

• Discovery and approval of new, non-addictive, pain medications has been disappointing.
• Pain perception is subjective
• Placebo effects are common
• Translation from animal models to human has been poor
• Addiction mechanisms are not well understood.
• Genetic pre-disposition
• Childhood trauma
• Environmental factors
• To end the opioid crisis, scientific research aimed at discovering alternatives to opioids

and elucidating the mechanisms of addiction is required.

• Pain and addiction biomarkers are urgently needed
• New molecular approaches for treating pain are of premiere importance
• More options for MAT and reversal of overdose are crucial

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Biomarker Research

• NCWR has unique access to nearly 50,000 bio-samples from consenting patients.
• Samples obtained from ~2003-2015 in over 30 clinical protocols
• Tested drugs include opioids and non-opioids (time-course)
• Blood, DNA, and RNA are cross-referenced to non-confidential patient records
• Planning is underway to extend this research asset by collecting additional bio-samples during MAT in the future
• Research strategies and identification of collaborators and scientific advisors in progress.
• Internal assessments of existing and future NCWR core competencies
• Data mining and visualization tools are under consideration
• Complementary industrial and academic partners enhance and accelerate NCWR’s mission
• Successful research will have broad and significant medical impact.
• Translational bio-markers will stimulate new research for opioid alternatives
• Pain bio-marker would supplement self-report measures in clinical trials, improving trial outcomes
• Predictive bio-markers for risk and/or onset of addiction would benefit patients and physicians

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β-Arrestin

Opioid

Mu Receptor G Protein

Analgesia Unwanted Effects

New Opioid Pharmacology

Pain Research

1800-1965

PIONEERING OPIOID CHEMISTRY

1970-2020

PIONEERING OPIOID BIOLOGY

Morphine, oxycodone, fentanyl, buprenorphine Mu receptor, enkephalin, cell signaling, biotech Analgesia

Opioid

Mu Receptor CELLULAR SIGNALING

X

BIASED OPIOID

• The discovery of opioid drug molecules does not overlap in

time with the discoveries about their mechanism.

• It has always been presumed that opioid analgesia and unwanted

effects are inseparable.

• Unpublished, “biased opioid” research molecules at NCWR show

analgesic efficacy with reductions in unwanted effects in animal models.

• Molecules in this collection may also lead to new MAT treatment
• ptions
• NCWR is well positioned to advance the science in this area and

make new discoveries that will benefit patients. Opioid Pharmacology

Gastrointestinal Respiratory Euphoria

+

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NCWR-1: A Novel Pre-Clinical Research Molecule with Biased Mu Receptor Signaling

Dose (mg/kg) % Maximum Possible Effect (Hot Plate)

• 50
• 25

25 50 75 100 Vehicle 1 3 10 30 100

Dose (mg/kg) % Maximum Possible Effect (Hot Plate)

• 50
• 25

25 50 75 100 Vehicle 1 3 5 10

Minimally Effective Analgesic Dose Minimally Effective Analgesic Dose Constipation Constipation Respiratory Depression Respiratory Depression 1hr time point, s.c. dosing 3hr time point, p.o. dosing

MORPHINE NCWR-1

• The onset of important opioid side-effects differ significantly between morphine

and NCWR-1 in animal models, despite both being mu receptor agonists.

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Fighting the Emerging Fentanyl Crisis

• The 3rd wave of the opioid crisis is fueled by fentanyl
• Fentanyl is particularly dangerous
• Mu receptor affinity and duration of action exceed naloxone
• ”Designer” analogs of fentanyl are evasive to law enforcement
• Inexpensive to prepare without need of opium poppies
• Blended into other drugs of abuse without knowledge of the end-user.
• Research molecules at the NCWR have profiles that may lead to

effective alternative treatments for fentanyl overdose

• Higher affinity to mu opioid receptor
• High CNS penetration
• Long duration of action

Molecule Mu Opioid Receptor Lipophilicity Half-Life

Ki (nM) GTPγS EC50 (nM) GTPγS EMAX (%) AlogP Hours

Fentanyl 2.7 133 88 4.05 4-8 Naloxone 8.8 >20000 2.1 0.5 – 1.5 NCWR-2 0.3 >20000 2.7 10 - 12 NCWR-3 0.9 >20000 3.49 TBD NCWR-4 0.07 >20000 3.88 TBD NCWR-5 0.07 >20000 6.07 TBD NCWR-6 0.4 >20000 5.13 TBD

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“Fighting Fire-With Fire”: Research Agreements in Progress with Industry

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Oral thin film formulation High-sensitivity fentanyl bio-sensor

National Center for Wellness & Recovery

“To inspire hope and to develop innovative, science-driven treatment interventions to improve the lives of those afflicted by pain and substance use disorders”

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MISSION

• Biomarker research for pain and addiction
• Novel mechanisms for pain and MAT treatment
• New molecules, delivery systems, and analytical

tools to combat the emerging fentanyl crisis

Presentation Summary

Oklahoma Bureau of Narcotics

SEPTEMBER 10, 2020

Integration and E-prescribing

• STATUS OF INTEGRATION
• 139 ENTITIES IN THE PROCESS OF INTEGRATING
• OVER 5,300 PRESCRIBERS BEING INTEGRATED
• STATUS OF ELECTRONIC PRESCRIBING
• 88% OF PRESCRIPTIONS ARE SUBMITTED ELECTRONICALLY
• 5.19% OF PRESCRIPTIONS ARE WRITTEN

Written, 5.19% Electronic, 88.39% 0.00% 10.00% 20.00% 30.00% 40.00% 50.00% 60.00% 70.00% 80.00% 90.00% 100.00% Jan-17 Feb-17 Mar-17 Apr-17 May-17 Jun-17 Jul-17 Aug-17 Sep-17 Oct-17 Nov-17 Dec-17 Jan-18 Feb-18 Mar-18 Apr-18 May-18 Jun-18 Jul-18 Aug-18 Sep-18 Oct-18 Nov-18 Dec-18 Jan-19 Feb-19 Mar-19 Apr-19 May-19 Jun-19 Jul-19 Aug-19 Sep-19 Oct-19 Nov-19 Dec-19 Jan-20 Feb-20 Mar-20 Apr-20 May-20 Jun-20 Jul-20 Aug-20 Sep-20

Prescription Submission Type

Written Electronic Fax Telephone Unspecified

PMP Statistics

2020 year to date Opioids 2,416,694 45.3% Non-Opioid 2,917,528 54.7% Total 5,334,222 100%

Schedule 2 43% Schedule 3 12% Schedule 4 40% Schedule 5 5%

DISPENSATION BY DRUG SCHEDULES

Schedule 2 Schedule 3 Schedule 4 Schedule 5

2020 year to date HYDROCODONE 977,142 18.3% OXYCODONE 485,807 9.1% TRAMADOL 391,994 7.3% ALPRAZOLAM 384,804 7.2% ZOLPIDEM 312,827 5.9% Total 2,552,574 47.8%

PMP Statistics

9145506 8388189 7597205 5334222 8959043 8163327 7338985 5136904 1000000 2000000 3000000 4000000 5000000 6000000 7000000 8000000 9000000 10000000 2017 2018 2019 2020

Total Rx per Year

W/ Buprenorphine W/out Buprenorphine

Opioid Statistics

4627292 4132423 3573979 2416694 4440829 3907561 3315759 2219376 500000 1000000 1500000 2000000 2500000 3000000 3500000 4000000 4500000 5000000 2017 2018 2019 2020

Total Opioid Rx per Year

W/ Buprenorphine W/out Buprenorphine

Disclaimer

• All data was pulled September 9, 2020.
• Data is labeled by whether it includes Buprenorphine.
• Data is entered by the pharmacy and errors could occur.

LEGISLATIVE UPDATE 9/10/20

Deputy Attorney General Lori Carter

HOUSE BILLS

• HB4138 by Representative Kevin Wallace and Senator Roger

Thompson

• Creates the Opioid Abatement Revolving Fund and the Opioid Abatement

Board to disperse opioid grant awards to political subdivisions for the purpose

• f abating the opioid crisis in Oklahoma
• Signed by the Governor on May 21, 2020/effective date August 28, 2020
• HB4140 by Representative Kevin Wallace and Senator Roger

Thompson

• Appropriates $10.22 million from the Opioid Lawsuit Settlement Fund to the

Oklahoma Opioid Abatement Revolving Fund, as created by HB4138

• Signed by the Governor on May 21, 2020/effective date August 28, 2020

SENATE BILLS

• SB1718 by Senator John M. Montgomery and Representative Jon Echols
• Parity legislation - It requires benefits for mental health conditions and substance use

disorders be equal to benefits for treatment of all other conditions and shall be subject to the same preauthorization and utilization review mechanisms and other terms and conditions as all other physical diseases and disorders.

• Requires health insurers to meet federal parity guidelines
• Requires insurers to file an annual report with the Insurance Commissioner to demonstrate

compliance with state and federal parity laws

• Requires Insurance Commissioner to enforce the parity laws and shall post online redacted

reports submitted and identify noncompliant insurers

• Status: Signed by the Governor May 19, 2020/effective Nov. 1, 2020
• SB1915 by Senator Kim David and Representative John Pfeiffer
• Amends the Physician Assistant Act to provide for physician “delegation” instead of

“supervision” and authorizes physician assistants to provide health care services, provided a practice agreement with an allopathic or osteopathic physician or physicians is in place

• P

.A. is to be considered the primary care provider and services must be reimbursed the same as if a physician had ordered or provided them

• Status: Signed by the Governor May 21, 2020/effective Aug. 28, 2020

INTERIM STUDIES & NEXT SESSION

• IS20-023 by Representative Cindy Munson
• Will look at the availability of over-the-counter loperamide (Imodium) – opioid-based
• September 15, 2020 in Room 206, 9am-11am
• Sickle Cell Anemia bill

OTHER UPDATES

• Opioid Overdose Fatality Review Board
• Virtual Meeting October 16, 2020 at 1:00pm
• OSU Center for Wellness and Recovery
• State of Addiction Virtual Conference September 9-11, 2020

NEXT MEETING

• Oklahoma Commission on Opioid Abuse
• November 10, 2020 (possibly virtual) at 1:30pm Attorney General’s Office
• Final Report Due: December 31, 2020